Alizadeh, ValiGarcia Santos, IsabelCastiñeiras, AlfonsoMahmoudi, GhodratSafin, Damir A2025-04-182025-04-182024Alizadeh, V., Garcia-Santos, I., Castiñeiras, A., Mahmoudi, G., & Safin, D. A. (2024). A pyrazinamide-benzenesulfonohydrazide hybrid N'-(phenylsulfonyl) pyrazine-2-carbohydrazonamide: experimental and theoretical insights. Tetrahedron, 134066.10.1016/j.tet.2024.134066http://dx.doi.org/10.1016/j.tet.2024.134066https://hdl.handle.net/20.500.12713/6596A pyrazinamide-benzenesulfonohydrazide hybrid N'-(phenylsulfonyl)pyrazine-2-carbohydrazonamide (1), which was studied by physical measurements and computational tools, is reported. Compound 1 was synthesized using a metallic Na-assisted interaction of 2-cyanopyrazine with benzenesulfonylhydrazine in dry methanol. Our newly developed synthetic approach allowed to obtain the title compound witht the yield of 74%, which is more than twice higher in comparison to the previously reported synthesis using pyrazine-2-carbohydrazonamide and benzenesulfonyl chloride. Molecules of the title compound are linked via N–H⋯O, C–H⋯Ph, S=O⋯2-pyrazine and π⋯π interactions. As it was found by the Hirshfeld surface analysis, molecules of 1 interact through H⋯X (X = H, C, N and O) contacts. Electronic properties of 1 were revealed using the Density Functional Theory (DFT) computations. 1 was expected to be a fourth-class toxicity, and it does not penetrate the blood-brain barrier, while can potentially be absorbed by the gastrointestinal tract. It was predicted that compound 1, which demonstrated the strongest activity against PLpro, Nsp3_range 207–379 MES and Nsp16_SAM site, are of interest to suppress activity of the SARS-CoV-2 proteins. Although the Ki value is slightly higher, the ligand efficiency scores for complex PLpro–1 were found to be characteristic for a Hit. © 2024 Elsevier Ltdeninfo:eu-repo/semantics/closedAccessADMETBenzenesulfonylhydrazineDFTHirshfeld Surface AnalysisPyrazineX-RayArticle162WOS:0013253270000012-s2.0-85196283998Q210.1016/j.tet.2024.134066Q3